5MM4

Ustilago maydis kinesin-5 motor domain in the AMPPNP state bound to microtubules

Summary for 5MM4

• Entry DOI: 10.2210/pdb5mm4/pdb
• EMDB information: 3529
• Descriptor: kinesin-5, Tubulin alpha-1A chain, Tubulin beta chain, ... (8 entities in total)
• Functional Keywords: ustilago maydis, kinesin-5, motor protein
• Biological source: Ustilago maydis (strain 521 / FGSC 9021); More
• Total number of polymer chains: 3
• Total formula weight: 141189.34

Authors

Moores, C.A.,von Loeffelholz, O. (deposition date: 2016-12-08, release date: 2018-06-27, Last modification date: 2024-05-15)

Primary citation

von Loeffelholz, O.,Ann Moores, C.
Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules.
J.Struct.Biol., 2019

PubMed Abstract: In many eukaryotes, kinesin-5 motors are essential for mitosis, and small molecules that inhibit human kinesin-5 disrupt cell division. To investigate whether fungal kinesin-5s could be targets for novel fungicides, we studied kinesin-5 from the pathogenic fungus Ustilago maydis. We used cryo-electron microscopy to determine the microtubule-bound structure of its motor domain with and without the N-terminal extension. The ATP-like conformations of the motor in the presence or absence of this N-terminus are very similar, suggesting this region is structurally disordered and does not directly influence the motor ATPase. The Ustilago maydis kinesin-5 motor domain adopts a canonical ATP-like conformation, thereby allowing the neck linker to bind along the motor domain towards the microtubule plus end. However, several insertions within this motor domain are structurally distinct. Loop2 forms a non-canonical interaction with α-tubulin, while loop8 may bridge between two adjacent protofilaments. Furthermore, loop5 - which in human kinesin-5 is involved in binding allosteric inhibitors - protrudes above the nucleotide binding site, revealing a distinct binding pocket for potential inhibitors. This work highlights fungal-specific elaborations of the kinesin-5 motor domain and provides the structural basis for future investigations of kinesins as targets for novel fungicides.

PubMed: 31288039
DOI: 10.1016/j.jsb.2019.07.003

Experimental method

ELECTRON MICROSCOPY (4.5 Å)